Cataplexy hypocretin

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, may be caused by the lack of hypocretin mRNA and peptides in humans (Peyron et al., 2000) or a disruption of the hypocretin receptor 2 or its ligand in dogs and mice (Lin et al., 1999 Chemelli et al., 1999). Hypocretin-containing neurons are located exclusively in the dorsomedial, lateral, and perifornical hypothalamic areas (Peyron et al., 1998). Two hypocretin sequences, Hcrt-1 (orexin-A) and Hcrt-2 (orexin-B), are generated from a single preprohypocretin (De Lecea et al., 1998 Peyron et al, 1998 Sakurai et al, 1998). Axons from these neurons are found in the hypothalamus, locus coeruleus (LC), raphe nuclei, tuberomamillary nucleus, midline thalamus, all levels of spinal cord, sympathetic and parasympathetic centers, and many other brain regions... 

Thakkar, M. M Ramesh, V., Cape, E. G. et al. (1999). REM sleep enhancement and behavioral cataplexy following orexin (hypocretin)-II receptor antisense perfusion in the pontine reticular formation. Sleep Res. Online 2, 112-20. 

Mieda, M. Yanagisawa, M. (2006). Rodent models of narcolepsy-cataplexy. In The Orexin/Hypocretin System Physiology and Pathophysiology, ed. S. Nishino T. Sakurai, Totowa, NJ Humana Press, pp. 255-66. 

The main risk factor appears to be a genetic susceptibility to the illness. The majority of narcolepsy patients, particularly those with cataplexy, have a genetic marker known as HLA-DQB1 0602. Recent evidence indicates that the key dysfunction in narcolepsy is diminished activity of a newly discovered neurotransmitter known as hypocretin. This new evidence has led to the development of a new diagnostic test for narcolepsy and may ultimately lead to new treatments that act directly on hypocretin systems in the brain. 

Kanbayashi T, Inoue Y, Chiba S, Aizawa R, Saito Y, Tsukamoto H, Fujii Y, Nishino S, Shimizu T (2002) CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia. J Sleep Res 11 91-93... 

Kambayashi T, Abe M, Fujimoto S, Miyachi T, Takahashi T, Yano T, Sawaishi Y, Arii J, Szilagyi G, Shimizu T (2003) Hypocretin deficiency in Niemann-Pick type C with cataplexy. Neumpediatrics 34 52-53... 

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